Background/Purpose: Etanercept (ETN) is approved for the treatment of pediatric patients with the polyarticular subtype of juvenile idiopathic arthritis (JIA). In addition, based on the interim 12-week data from the first part of the CLIPPER study,¹ ETN was recently approved in the EU for the treatment of pediatric patients with the extended oligoarticular (eo), enthesitis-related (ERA), and psoriatic (PsA) JIA subtypes. The majority of studies performed with ETN to date have enrolled subjects with polyarticular-onset JIA and limited information is available on the eoJIA, ERA, and PsA JIA subtypes. The objective of the second part of the CLIPPER study was to assess the long-term safety and clinical benefit of ETN in pediatric subjects with these JIA subtypes.

Methods: CLIPPER was a 96-week, Phase 3b, open-label, multicenter study. Subjects with eoJIA (2–17 years old), ERA (12–17 years old), or PsA (12–17 years old) received ETN 0.8 mg/kg once weekly (maximum dose 50 mg) for 96 weeks. Safety was assessed by reporting treatment-emergent adverse events (TEAEs) and serious TEAEs throughout the study. Efficacy endpoints included the proportions of subjects achieving JIA American College of Rheumatology (ACR) 30/50/90 responses and inactive disease criteria at Week 96.

Results: 127 subjects (eoJIA n=60, ERA n=38, PsA n=29) received ≥1 dose of ETN.  Mean age was 11.7 (SD, 4.5) years and disease duration was 26.8 (SD, 26.4) months. Safety results are summarized in the table. Most frequently reported TEAEs were (number of events, events per patient year [EPPY]): headache (23, 0.107), pyrexia (12, 0.056), diarrhea (10, 0.046), leukopenia (8, 0.037), increased alanine aminotransferase (8, 0.037), and arthralgia (8, 0.037). The most commonly reported treatment emergent (TE) infections were (number of events, EPPY): upper respiratory tract infection (83, 0.386), pharyngitis (50, 0.232), gastroenteritis (22, 0.102), bronchitis (19, 0.088), and rhinitis (17, 0.079). No cases of malignancy, active tuberculosis, demyelinating disorders, or deaths were reported. At Week 96, the overall proportions (95% CI) of subjects achieving JIA ACR 30/50/90/inactive disease criteria were 99.1% (94.9, 100), 98.1% (93.5, 99.8), 65.4% (55.6, 74.4), and 34.0% (25.0, 43.8), respectively. Approximately a 2-fold and 3-fold increase in the percentage of JIA ACR 90 and inactive disease responders from Week 12 to Week 96, respectively, was noted.

Conclusion: ETN treatment for 96 weeks was well-tolerated and effective in treating subjects with the JIA subtypes, eoJIA, ERA, or PsA, as expected from the previous data from polyarticular JIA.

Reference: 1. Horneff G, et al. Ann Rheum Dis 2013;0:1–9. doi:10.1136/annrheumdis-2012-203046